KUBOTA, K., KUBOTA, R. and MATSUZAWA, T. Growth and Differentiation ofTeratocarcinoma OTT6050 Affected by Host Hormonal Changes in Old Mice. Tohoku J. exp. Med., 1987, 151(3), 253-259-We previously reported the age and sex dependent decrease in the growth rate of teratocarcinoma OTT6050. Studies of the effects of hormones on the tumor growth are presented here. Age related changes in the serum levels of triiodothyronine, thyroxine, progesterone, testosterone and estradiol that increase in the young adult and decrease in the old were observed with radioimmunoassay. Administration of estradiol to tumor-bearing, 50 week-old female mice increased the tumor growth rate to that of 10 week-old mice. Tumor growth rates in estradiol-treated 10 week-old female and male mice were slightly accelerated compared to the control, but not as fast as that of control juveniles. It can be concluded that extrinsic estradiol stimulates the teratocarcinoma growth in vivo especially in old female mice. Age-dependent decline of the growth rate of teratocarcinoma in the female is due partly to changes in estrogen level.
KUBOTA, K., YAMAGUCHI, T., FUJIWARA, T. and MATSUZAWA, T. Effects ofSmoking on Regional Cerebral Blood Flow in Cerebral Vascular Disease Patientsand Normal Subjects. Tohoku J. exp. Med., 1987, 151(3), 261-268-The chronic effect of smoking on the regional cerebral blood flow (r-CBF) was studied by 133-Xenon inhalation method and described with the Initial Slope Index (ISI). Fifty-two patients as the control group who had no abnormality neurologically or with CT scan, 32 patients with old cerebral infarction and 20 patients with old cerebral hemorrhage were introduced to the present study, and these patients were divided into smokers and non-smokers in each group. Those whose smoking index of 200 or more [(number of cigarettes/day)×(years of smoking history)≥200] were designated as smokers. ISI values were decreased significantly in smokers than non-smokers in all groups. Mean ISI value of unaffected hemisphere in smokers decreased by 16% in the infarction group and 22% in the hemorrhage group comparing to the non-smokers', respectively. In the control group, mean ISI value of right hemisphere decreased by 15% and left 14% in smokers compared to the non-smokers. The r-CBF values in 44 of the 47 smokers were found to be lower than the expected age matched values in non-smokers. Serum high density lipoprotein cholesterol value in smokers was significantly lower than that in non-smokers. We demonstrated preliminarily that the smoking chronically reduced the r-CBF. Advanced atherosclerosis associated with the smoker wassuggested to affect the CBF.
YAJIMA, Y., OTSUKI, M., SUZUKI, H., MORI, K. and GOTO, Y. A Case of LiverCirrhosis Complicated with Endotoxemia and Disseminated Intravascular Coagulation:A Case Report. Tohoku J. exp. Med., 1987, 151 (3), 269-274-A 59-year-old female was admitted to our hospital because of massive ascites and increasing jaundice, suggesting a severe decompensated state of liver cirrhosis. On the third hospital day, she was diagnosed as disseminated intravascular coagulation (DIC) from a coagulofibrinolytic study and developed renal failure. Continuous drip infusion of gabexate mesilate, a synthetic inhibitor of serine-protease, was found to be successful in managing DIC, followed by the restoration of renal function. During the clinical course, blood endotoxin, assayed by the chromogenic method, was initially 11pg/ml and increased, in accordance with the elevation of serum FDP, to a level of 110pg/ml when renal failure occurred. A proportional relationship was observed between changes in blood endotoxin and serum FDP throughout the course. This finding may be an important clue in studying the mechanism of DIC and non-septic endotoxemia both developing in liver cirrhosis.
KOIZUMI, F., KAWAMURA, T., ISHIMORI, A., EBINA, H. and SATOH, M. Correlation between Gastric Emptying Time and the Response of PancreaticPolypeptide to Test Meals in Peptic Ulcer Diseases. Tohoku J. exp. Med., 1987, 151(3), 275-281-In the present study, pancreatic polypeptide (PP) levels both in basal state and after stimulation by meal were determined in 21 controls, 28 patients with gastric ulcer and 21 patients with duodenal ulcer and their correlation with gastric emptying was examined. In patients with gastric and duodenal ulcers, basal levels as well as stimulated of plasma PP during 95min of observation period were higher than those in controls except for the values at 5min. As no correlation was seen between integrated PP response (IPPR) to the meal and T1/2 for gastric emptying in any of three groups, it was indicated that gastric emptying has only a minor role in postprandial PP response.
MINEGISHI, M., TSUCHIYA, S., MINEGISHI, N. and KONNO, T. Establishment ofFive Human Malignant Non-T Lymphoid Cell Lines and Mixed Lymphocyte-Tumor Reaction. Tohoku J. exp. Med., 1987, 151(3), 283-292-Five human malignant non-T lymphoid cell lines have been established. THP-4 and THP-7 were derived from two children with common type acute lymphoblastic leukemia (ALL), THP-6 and THP-8 from two children with null cell type ALL and THP-9 from a child with malignant lymphoma. THP-4 was positive for cytoplasmic μ, B4, common ALL antigen (CALLA) and Ia-like antigen (Ia), THP-7 positive for B4, CALLA and Ia, THP-8 positive for B4 and Ia, and THP-9 positive for surface μ-λ, B1, B4, CALLA and Ia. No antigenic determinants for monoclonal antibodies used were detected on THP-6. THP-4, THP-7, THP-8 and THP-9 were able to stimulate allogeneic lymphocytes vigorously. THP-6 without Ia stimulated not only allogeneic lymphocytes, but also autologous ones. THP-7 did not stimulate autologous lymphocytes.
YAMAGUCHI, S., ORII, T., YASUDA, K. and KOHNO, Y. A Case of GlutaricAciduria Type I with Unique Abnormalities in the Cerebral CT Findings. Tohoku J. exp. Med., 1987, 151(3), 293-299-A first Japanese case of glutaric aciduria type I (GA-I) was described. She was a 7-month-old girl presenting with poor head control, irritability and sleeplessness. The profile of urinary organic acids by gas chromatography mass spectrometry (GC/MS) suggesting GA-I were confirmed by no activity of glutaryl-CoA dehydrogenase in the fibroblasts. The cerebral computer tomography (CT) showed marked changes such as large fluid collections on bilateral frontotemporal regions and a slight enlargement of bilateral ventricles. The amounts of urinary glutarate excretion decreased after restriction of lysine and tryptophan in her diet and administration of carnitine improved the carnitine levels in blood and urine, while these were less effective for the neurological symptoms. On the other hand, oral administration of lioresal, an analogue of gamma-aminobutyrate (GABA), cleared her symptoms such as ill temper, irritability and sleeplessness dramatically, and the abnormalities of the CT examinations were not more deteriorative until 2 years of her age at least. The neurological manifestations of GA-I seemed to be affected by the unusual metabolism of GABA in the central nervous system.
MIZUTANI, N., HAYAKAWA, C., MAEHARA, M. and WATANABE, K. EnzymeReplacement Therapy in a Patient with Hyperargininemia. Tohoku J. exp. Med., 1987, 151(3), 301-307-In a patient with hyperargininemia, enzyme replacement therapy such as whole blood exchange transfusion or erythrocyte transfusion was performed, and its effect was confirmed in vitro as well as in vivo. The patient has been treated with the restriction of protein intake, oral administration of an essential amino acid mixture, and sodium benzoate or phenylacetic acid. With these treatments, his plasma ammonia levels were controlled. On the other hand, plasma and CSF concentrations of arginine were not so well controlled. With whole blood exchange transfusion and erythrocyte transfusion, plasma arginine concentrations and plasma ammonia levels were controlled. These effects have continued for about 3 months. Furthermore, the effect of exchanged erythrocytes on the blood arginine levels was also confirmed by in vitro experimentation that mixes arginine with erythrocytes in the medium RPMI 1640. Arginine concentration of the medium did not decrease when arginine was mixed with erythrocytes of the patient, but when arginine was mixed with erythrocytes of mother or normal controls, it decreased rapidly. In calculation, 107 of erythrocytes of the mother or normal controls was presumed to metabolize 4-5 nmole of arginine per day. From these results, the erythrocyte exchange transfusion is considered to be effective for the control of clinical and biochemical abnormalities in this disorder.
HIRAI, N., HATTORI, N., HILL, N.O. and OSTHER, K. Antiproliferative Assayof Human Leucocyte Interferon. Tohoku J. exp. Med., 1987, 151(3), 309-316-An in vitro microtitration system of the antiproliferative effect of human leucocyte interferon (IFN-α(Le)) was investigated. The preliminary experiments suggested that the antiproliferative effect of IFN-α(Le) was increased by prolonging the incubation period, by reducing the target cell concentration, and might be prescribed by the total IFN amounts in the challenge medium. By employing a system consisted of 1.5×104 Daudi cells in 0.2ml of medium containing IFN dilutions and an incubation period of 3 days at 37°C, the antiproliferative effects of twenty-one lots of partially purified IFN-α(Le) (PIF-α(Le)) preparations were titrated. The interassay variations in the antiproliferative titers of three PIF-α(Le) established in the present system were found to be in the same range as those in the antiviral titers estimated by a standard macroplaque reduction assay. The each titration curve was parallel, and the antiproliferative titers, assessed by the reciprocals of the IFN dilutions which suppress the cell growth in 50%, were significantly (p<0.01) correlated to the antiviral international units of them.
KOMATSU, N., KIDO, A. and OYA, M. Polymorphism of ACP1 by IsoelectricFocusing: Population Study in Japanese and Phenotyping in Bloodstains. Tohoku J. exp. Med., 1987, 151(3), 317-321-The polymorphism of ACP1 was investigated in 749 unrelated Japanese individuals by isoelectric focusing. The allele frequencies were ACP1*A=0.2083 and ACP1*B=0.7917, which were almost similar to those reported in other Japanese subpopulations. The isoelectric focusing technique was successfully applied to ACP1 typing in bloodstains; each phenotype was demonstrated at 37°C for up to 4 weeks, at room temperature for up to 10 weeks and at 4°C for over 16 weeks after stain formation. The isoelectric focusing method proved more useful than conventional electrophoretic methods in medicolegal practice.
TAKASE, S., OHARA, Y., NOMURA, H., OKITA, N., NAKANO, S., KOGURE, K. and ITAHARA, K. Comparative Studies on Clinical Features and CASE Proteins ofMotor Neuron Disease Patients. Tohoku J. exp. Med., 1987, 151(3), 323-331-Clinical features such as types of diseases, sex ratio, age of onset, sites of initial involvement, the appearance of bulbar signs, and duration of illness were studied in 52 patients with motor neuron disease (MND) with a special reference to immunoglobulin in cerebrospinal fluid (CSF) and serum. Although MND has been thought to be a degenerative disease of unknown cause, our data suggested there are some immunological abnormalities in this disease. The duration of illness and the abnormalities of CSF immunoglobulins appeared to be correlated with the type of disease and the site of initial involvement. However, whether or not these abnormalities in CSF immunoglobulins are directly related to the pathogenesis of MND remains unclear.
SAJIKI, N. and NAKAMURA, R. Effect of Passive Motions on the Initiation ofFast Knee Extension in Patients with Paraparesis. Tohoku J. exp. Med., 1987, 151(3), 333-338-Using reaction time paradigm, the effect of repetitive passive motion (RPM) on the initiation of fast knee extension was analyzed in seven normal subjects and 10 patients with paraparesis. Before and after 5min RPM of the responding lower extremity, i.e., alternate flexion and extension of the knee and the hip with frequency of 0.5Hz, the following five variables were examined: premotor time (PMT), latency from sound stimulus to initiation of EMG activities of the rectus femoris; tension lag time (TLT), period between onset of EMG activities and rise of tension; contraction time (FTmax); maximum tension (Tmax); and rate of tension development (RTD, Fmax/FTmax). In the normal group, PMT decreased significantly after RPM, whereas the other four variables did not show any change due to RPM. In the patient group, shortening of both PMT and FTmax after RPM was significant and Fmax tended to be small. These results suggested that RPM of an extremity induces behavioral alertness when the afferent pathway from moving parts to the higher center is not interrupted and also that RPM modulates abnormal pattern of motor neuron activities at the spinal level.
ISHII, M., SUZUKI, H., KOBAYASHI, K., MIYAZAKI, Y., OTSUKI, M. and GOTO, Y. An Improved Method for Observing the Cytoskeleton around the Bile Canaliculi ofRat Hepatocytes. Tohoku J. exp. Med., 1987, 151(3), 339-344-In order to know more about the cytoskeletal structure around the bile canaliculi of hepatocytes, we used the following procedure. Liver specimens were passed through an 18-, a 21- and then a 23-gauge needle, by which they turned into cylindrical or oval blocks of 0.4mm in diameter. Because of their small size, the cytosolic ground substances of every hepatocyte were washed out clearly after subsequent treatment with the solution containing 0.5% Triton X-100 and 0.5mg/ml saponin for 15min. This short-term extraction preserved both the cytoskeleton and the plasma membrane of the hypatocyte quite well, and we could observe the cross-bridge filaments connecting between a core bundle of microfilaments and plasma membrane of the microvilli of the bile canaliculi.
KYONO, K. A Study of the Fertilizing Capacity of Human Spermatozoa:The Hamster Test. Tohoku J. exp. Med., 1987, 151(3), 345-349-There are many reports on the hamster test as a test of the fertilizing capacity of human spermatozoa, and its usefulness is widely known. However, the results obtained cannot be simply compared because of the different conditions used for the test. According to our studies, the type of serum albumin present in incubated specimens was considered to affect particularly the rate of sperm penetration. Penetration rates of human spermatozoa were determined under the most appropriate test conditions using good-quality human serum albumin. The penetration rate was 69±9% (range: 33-98%) in men whose fertility had been confirmed within 2 years before test, while it was 34±5% (range: 0-100%) in infertile men, showing a significantly low rate. Eight of nine men who achieved fertilization within one year after the examination showed a penetration rate of over 30%. The remaining one showed a rate of 16%, but he underwent surgery for varicocele and treatment with methylcobalamin and Hochuekkito after the test. Men thus seem difficult to conceive women when the penetration rate of their spermatozoa is below 30%.
SASAKI, I., KONNO, Y., KAMIYAMA, Y. and SATO, T. Acute Gastric Ulcerationin Rats with Obstructive Jaundice with Special Reference to Gastric Mucosal BloodFlow. Tohoku J. exp. Med., 1987, 151(3), 351-358-The mechanism of acute gastric ulceration in rats with obstructive jaundice was investigated in terms of the changes in the gastric mucosal blood flow, and the effect of vagotomy on ulceration was examined. 188 Sprague-Dawley rats weighing about 250g were prepared and divided into 4 groups as follows; control group (sham operation), jaundiced group (ligation of the bile duct), vagotomized group (vagotomy with pyloroplasty), jaundiced and vagotomized group (simultaneous ligation of the bile duct and vagotomy with pyloroplasty). Two weeks after the operation, water immersion and restraint stress procedures were performed in these 4 groups. The gravity of acute gastric ulcerations was calculated by ulcer index. The gastric mucosal blood flow was measured by hydrogen clearance technique. The following results were obtained: In control group, ulcer index was increased and gastric mucosal bloodflow was decreased after the stress procedures. The jaundiced group showed significantly higher ulcer index and early significant decrease of gastric mucosal blood flow after the stress procedures compared to the control group. The vagotomized group showed significantly decreased ulcer index after the stress procedures compared to the control group, however, the gastric mucosal blood flow showed almost the same values as the control group. The jaundiced and vagotomized group showed significant decrease of ulcer index and improvement of decrease of gastric mucosal blood flow compared to the jaundiced group. These results indicated that the gastric mucosal blood flow plays an important role in the occurence of acute gastric ulceration in rats with obstructive jaundice, and vagotomy might be useful to prevent them by maintaining gastric blood flow in obstructive jaundice.
CHIBA, S., TSUKADA, M., KATSUYAMA, Y., TADA, A. and ZENDA, H. PotentVasoconstrictor Responses to Endogenous Digitalis-Like Factor of Isolated, PerfusedDog Intermediate Auricular Arteries. Tohoku J. exp. Med., 1987, 151(3), 359-362 -Endogenous digitalis-like factor obtained from urine of hypertensive patients caused a vasoconstriction in a dose-related manner in isolated, perfused dog intermediate auricular arteries. The constriction was not modified by alpha-adrenoceptor blockade.